This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. These studies examine the functional interactions and the anatomy of the connections between the intralaminar nuclei of the thalamus (i.e., the centromedian and parafascicular nuclei (CM/PF)) and the striatum in normal and parkinsonian monkeys. CM and PF send a topographically organized projection to the striatum. Movement-related projections from the CM terminate in the putamen which may act to shape striatal output under normal and pathologic conditions. The CM/PF complex is empirically targeted for neurosurgical interventions, such as deep brain stimulation (DBS), in the treatment of patients with Tourette's syndrome and Parkinson's disease. We have found that electrical CM stimulation with short trains of stimuli results in complex sequences of activation and inhibition in striatal cells, which are most easily explained as the result of intrastriatal spread of activity and processing within the striatal circuitry, for instance through local inhibitory axon collaterals and cholinergic interneurons. The ongoing studies (started earlier this year) contrast striatal responses to CM/PF stimulation in normal and parkinsonian monkeys with a combination of electrophysiologic recordings, microinjections, and anatomic studies. In this funding period, we have started to reconstruct the anatomical inputs from CM to specific dendritic domains of cholinergic striatal interneurons (one of the major striatal recipients of CM inputs). In addition, we are studying CM inputs to chemically defined subtypes of striatal output neurons. Finally, we have started electrophysiological recordings in one animal to study the effects of electrical stimulation of the CM on the activity of cholinergic neurons in the striatum. The proposed studies will provide us with information regarding the anatomy and physiology of the thalamostriatal system, and its involvement in parkinsonism, will clarify the effects of electrical stimulation of CM, and will provide data to help clinicians optimize parameters for CM-DBS therapy in parkinsonian patients.